Current views on generation of antibody variability and differential expression of antibodies are derived principally from structure-function relationships among myeloma proteins and from information on the inheritance and variable expression of idiotypes, the individual antigenic determinants of antibody molecules. Conclusions about any mechanism depends finally on analysis of a set of clones for which markers for and sequences on binding and non-binding sites regions are obtainable. In such a system the ontogeny of B-lymphocytes secreting the antibodies and the influence of T-lymphocytes, of macrophages and of other unidentified regulatory cells and products on this developmental process can be made. In published experiments we have shown that the immune response to phosphorylcholine (PC) provides an appropriate model system. Inbred mouse strains, regardless of their genetic background, express three conserved clonotypes. This research proposes to evaluate the molecular heterogeneity of this set of clonotypes in mice and investigate certain specific regulatory mechanisms governing expression of individual members of this set. Analysis of these parameters will depend on isoelectric focusing of isolated antibodies and their constituent heavy (H) and light (L) chains, amino acid sequence analysis of H and L chains, use of variable region idiotypes, and genetic and cellular influences of V-region expression. These studies should provide basic information about the generation of antibody diversity and mechanisms responsible for regulating clonal expression.